A zero order release theophylline product, THEO-DUR, has received widespread acceptance in the marketplace and among the medical profession as a bronchodilator. However, THEO-DUR is in the form of a dry tablet formulation which cannot be easily swallowed by certain individuals. Specifically, children and elderly patients often have difficulty swallowing tablets. Accordingly, there is a need to provide a sustained release bronchodilator which is in a dry form, but which can be more easily administered to individuals having difficulty in swallowing, such as children and elderly patients. In addition, there is a need for a method for orally administering any such dry formulation in a manner which will be acceptable to children and elderly patients.
U.S. Pat. No. 3,344,029 to Berger et al discloses a sustained release composition which can include a theophylline salt as an active ingredient. Finely divided active ingredients such as theophylline salt can be mixed with a powdered sugar and corn starch. This mixture can be combined with other ingredients such as polyethylene glycol to form material which is forced through a mesh screen to form cores (see column 3, lines 5-30). The cores are then placed into a coating pan and are coated and dried (see column 3, line 55-column 5, line 30).
U.S. Pat. No. 3,109,775 discloses a theophylline-noscapine sustained released composition which is used in the treatment of asthma or other bronchial disorders. The composition can be comprised of an inner core which is coated with an inactive ingredient such as sucrose or cellulose combined with the active ingredients (see column 8, lines 36-54). A fat-wax can be utilized as a retardant to obtain sustained release of the active ingredients (see column 7, line 39).
U.S. Pat. No. 4,321,253 discloses a suspension of microencapsulated bacampicillin acid addition salt for oral, especially pediatric administration. The patent discloses the formation of micropellets which are placed into an aqueous suspension and then administered to a patient. Since the microcapsules are placed in an aqueous solution, the active ingredient can start being released to solution immediately and the amount of active ingredient released to the solution could increase with time. This could render the solution bitter and children may be reluctant to take such a "medicine". Furthermore, the accurate dosing of a suspension is more difficult to obtain, since the suspension is usually measured by a tea or tablespoon and a tea or tablespoon full made very widely in size. The inability to know the exact dose of the pharmaceutically active drug in combination with the inability to determine how much was released to the solution is a particularly big problem with respect to the drug theophylline which has a very narrow therapeutic window.
U.S. Pat. No. 3,835,221 discloses an orally administrable drug dosage form which has delayed action. The dosage form is comprised of small globules which are provided with a release-delaying coating. The active substance is applied to small inert essentially round globules which are coated in such a manner so as to provide delayed release of the active ingredient. The coating may include materials such as polyvinyl acetate which may be combined with another material such as ethyl cellulose.
U.S. Pat. No. 4,083,949 discloses a new oral form of medication and a method for producing it. The oral form disclosed releases the active ingredient in the gastrointestinal tract at a constant rate. The dosage form may be comprised of spheroidal shaped particles of active ingredient which are coated with materials such as ethyl cellulose in order to provide sustained release of the active ingredient.
Although each of the dosage forms described in the patents referred to above may offer advantages with respect to delivery the active ingredient to the patient, each of the disclosures does not take into consideration all of the factors which must be considered when attempting to provide the correct therapeutic blood level of theophylline to a young or elderly patient via an oral formulation. Accordingly, each of the above referred to formulations suffers from one or more disadvantages thus indicating a clear need for an oral dosage formulation such as that being presented herein by the present inventor.
As indicated above, THEO-DUR has received widespread acceptance in the marketplace and among medical professions. One of the main reasons for its widespread acceptance is that the THEO-DUR product provides a constant therapeutic blood level of theophylline. Accordingly, the desired bronchodilator effect is obtained, but the undesirable side effects from too much theophylline are avoided. The concept of the present invention is to provide the same zero order release concept with a product which can be more easily administered to patients who are reluctant to take tablets.